Retinitis Pigmentosa (RP): The Role of Oxidative Stress in the Degenerative Process Progression.

Purpose: Retinitis Pigmentosa is a term that includes a group of inherited bilateral and progressive retinal degenerations, with the involvement of rod photoreceptors, which frequently leads to blindness; oxidative stress may be involved in the degeneration progression as proposed by several recent studies. The goal of this study is to evaluate whether circulating free radicals taken from capillary blood are related to one of the most important features of Retinitis pigmentosa that can affect frequently patients: cystoid macular oedema (CME). Materials: A total of 186 patients with Retinitis Pigmentosa (range: 25−69 years) were enrolled; all patients completed an ophthalmologic examination and SD-OCT at baseline and were divided into three subgroups according to the SD-OCT features. ROS blood levels were determined using FORT with monitoring of free oxygen radicals. Results: Test levels of free oxygen radicals were significantly increased, almost twice, in RP patients showing cystoid macular oedema and significantly increased compared to the control group. (p < 0.001). Discussion: Our findings suggest that oxidative stress may speed cone photoreceptors' morphological damage (CMT); because long lasting oxidative stress in the RP may cause oxidative damage, with animal models of RP suggesting this is a micromolecular mechanism of photoreceptors' (cone) death, it can be similar to cone damage in human RP eyes. The limitations of this paper are the relatively small sample, the horizontal design of the study, and the lack of data about the levels of ROS in the vitreous body.

Clinical Features, Prognosis, and Long-Term Response to Ranibizumab of Macular CNVs in Pattern Dystrophies Spectrum: A Pilot Study.

INTRODUCTION: To analyze the morphological and functional features of choroidal neovascularizations (CNVs) in eyes affected by pattern dystrophies (PD), evaluating their long-term response to intravitreal ranibizumab, and comparing them with CNVs in age-related macular degeneration (AMD). The mean goal is to identify possible disease biomarkers and to evaluate the long-term prognosis of CNVs in PD. MATERIALS AND METHODS: A retrospective study of 42 patients with naïve CNV (26 PD and 16 AMD), for a total of 47 eyes (29 eyes in the PD group and 18 eyes in the AMD group). Each patient received a loading dose of ranibizumab (one monthly for three months) followed by pro re nata (PRN) reinjection protocol for a period of at least three years. Morphological OCT parameters (CRT, central retinal thickness; SRF, subretinal fluid; IRF, intraretinal fluid; SHRM, subretinal hyperreflective material; HRF, hyperreflective foci; HCD, hyperreflective crystalline deposits; cCT, central choroidal thickness; slCT, sublesional choroidal thickness; EZd, ellipsoid zone disruption; and best corrected visual acuity (BCVA in logMAR scale)) were reported at baseline and last follow-up. RESULTS: At baseline, no significant differences were found between the two groups, except for choroidal thickness parameters that were significantly greater in the PD group (p = 0.009). Longitudinal PD analysis demonstrated reduction in BCVA (p = 0.009), decrease in CRT (p = 0.046), resolution of SRF in 61.6% of cases (p = 0.004) and SHRM in 30% (p = 0.034), and choroidal thinning both centrally (p = 0.004) and sublesional (p = 0.011) compared to baseline. At 3 years, the PD group received significantly more injections than the AMD (p = 0.011) and showed significantly thicker choroid (p = 0.033) and more frequent HRF (p = 0.006). Regarding the PD group, we found a negative correlation between age and choroidal thicknesses at baseline and at 3 years (p < 0.05); significant positive correlations were found between baseline BCVA and at 3 years (p < 0.001), BCVA at 3 years and IRF (p = 0.003) and SHRM at 3 years (p = 0.003); CRT baseline and CRT 3 years (p = 0.017); HCD at 3 years was associated with greater CRT (p = 0.04) and IRF at 3 years (p = 0.019). CONCLUSIONS: Early and long-term morphofunctional features of CNVs in PD and in AMD are overlapping. CNVs in PD have poorer long-term response to ranibizumab and higher choroidal thickness suggesting different pathogenetic and evolutionary mechanisms.

PREDICTIVE FACTORS FOR DEVELOPMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Spectral-Domain Optical Coherence Tomography Study.

PURPOSE: To investigate the risk factors predictive for the development of neovascular age-related macular degeneration (NVAMD) by means of spectral-domain optical coherence tomography. METHODS: Retrospective study of 73 eyes graded Stage 2 and Stage 3 according to the AMD International Grading System with minimum follow-up of 24 months. Drusenoid pigment epithelial detachment, hyperreflective foci, external limiting membrane, inner ellipsoid band, and retinal pigment epithelium integrity were analyzed at baseline and last follow-up. Binary logistic regression model analyzed significant predictors of neovascular conversion. RESULTS: The discontinuity of external limiting membrane, inner ellipsoid band, and retinal pigment epithelium bands were significantly more prevalent in the NVAMD group at baseline and last follow-up (P < 0.001). Hyperreflective foci represented the single most important predictor of neovascular conversion (Exp [B], 15.15; P = 0.005) as confirmed by Kaplan-Meier curve (P = 0.002). Drusenoid pigment epithelial detachment width was significantly greater in NVAMD group than control subjects at baseline and last follow-up (P < 0.001), and its delta value also resulted a significant neovascular predictor (Exp [B], 0.99; P = 0.04). CONCLUSION: Hyperreflective foci significantly increase the risk of NVAMD progression. The delta width of drusenoid pigment epithelial detachment also predicts disease progression, integrating the stratification of NVAMD progression risk.

Clinical correlation between retinal sensitivity and foveal thickness in retinitis pigmentosa patients.

PURPOSE: To investigate the relationship between retinal structure and retinal sensitivity comparing data obtained using spectral-domain optical coherence tomography (SD-OCT) and microperimetry in retinitis pigmentosa (RP) and healthy patients. METHODS: A total of 49 patients (98 eyes) with RP were divided into 4 groups according to the OCT findings: group A, patients with no macular changes; group B, patients with cystoid macular edema (CME); group C, patients with vitreomacular traction (VMT); group D, patients with retinal thinning. As a control group, we enrolled 27 healthy subjects. All subjects underwent a complete ophthalmologic examination, including SD-OCT and microperimetry. For the statistical analysis, Pearson correlation test and linear regression analysis were used. A p value <0.05 was considered statistically significant. RESULTS: We did not find any significant difference in best-corrected visual acuity (BCVA), foveal thickness, or retinal sensitivity between group A and the healthy subjects (p>0.05). In group B, linear regression of logMAR versus foveal thickness and retinal sensitivity versus foveal thickness gave r values of 0.931 and 0.786, respectively. In group C, r values were 0.786 and 0.842, respectively, while in group D they were 0.816 and 0.795. CONCLUSIONS: This article shows the first application of the new microperimeter MP3 in patients with RP, which has proven to be very sensitive in detecting functional abnormalities in all the patients. Future studies should investigate the relationships among photoreceptor cell loss, retinal sensitivity, and fixation in patients with RP.

Visual Recovery after Primary Retinal Detachment Surgery: Biofeedback Rehabilitative Strategy.

Purpose. To evaluate possible speeding up recovery time after retinal detachment (RD) surgery using biofeedback strategy. Methods. A total of 52 eyes were selected. After surgery, patients were divided into two groups: group A, including patients submitted to biofeedback with MP-1 strategy; group B, patients who received common care strategy. Biofeedback strategy was started 15 days after the suspension of cycloplegic eye drops in buckling procedure or after silicone oil removal in the vitrectomized eyes. Controls were scheduled at baseline and 6, 12, and 18 weeks. Results. At baseline, there was no significant difference in BCVA between groups (P = 0.4230). At the end of biofeedback treatment (WK 6) BCVA of group A was significantly better (P < 0.001) than group B and BCVA was still better in group A than group B at WK 12 (P = 0.028) and at WK 18 (P = 0.041). Conclusions. Visual recovery after RD surgery is still unclear, and it does not depend on entity of the RD. Our data demonstrate that in biofeedback group there was a significant recovery in visual performances that still remains evident after 3 months from the baseline.

Fixation stability measurements in patients with neovascular age-related macular degeneration treated with ranibizumab.

OBJECTIVE: To evaluate which of 2 measuring units (bivariate contour ellipse area [BCEA] vs Fujii) yields more accurate measurements of fixation stability, obtained using the MP-1 device, in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab, during a 12-month follow-up period. DESIGN: Small retrospective, noncomparative, interventional case series. PARTICIPANTS: A total of 25 eyes in 25 patients (13 males, 12 females; mean age 71.72 ± 7.98 years). METHODS: All participants were older than 50 years, diagnosed with active subfoveal choroidal neovascularization, had best corrected visual acuity (BCVA) values above 20/100, and all lesion types were included. All patients underwent a loading phase with 3 consecutive intravitreal injections of 0.05 mg ranibizumab at monthly intervals. Patients were retreated after the third injection if they exhibited a 100-µm increase in macular thickness or evidence of intraretinal and/or subretinal fluid and new subretinal hemorrhage, observed with spectral-domain optical coherence tomography and fluorescein angiography. The data collected included BCVA and mean macular sensitivities, BCEA, and fixation patterns, performed at baseline and at months 4 and 12, using the MP-1 device. RESULTS: The mean total injection number was 5.92 ± 1.18 (minimum 3, maximum 8). Mean BCVA at baseline was 0.55 ± 0.28 logMAR and increased significantly to 0.50 ± 0.33 logMAR. Mean macular sensitivity at baseline was 7.06 ± 4.59 dB and increased significantly to 8.40 ± 4.82. Mean BCEA was 2.19 ± 1.38 deg(2) and decreased significantly to 1.68 ± 1.43 deg(2). Fixation stability patterns, according to the protocol set out by Fujii, did not change significantly during follow-up. CONCLUSIONS: Compared with Fujii fixation stability patterns, BCEA correlated better with variations in macular sensitivity and BCVA. BCEA can be added to the traditional parameters used to evaluate the efficacy of intravitreal injections in patients with nAMD.

Multifocal and pattern-reversal visual evoked potentials vs. automated perimetry frequency-doubling technology matrix in optic neuritis.

BACKGROUND: To compare the usefulness of the traditional pattern-reversal Visual Evoked Potentials (VEP) with multifocal VEP (mfVEP) and Frequency-Doubling Technology (FDT) perimetry in the evaluation of the ocular abnormalities induced by acute or subacute optic neuritis (ON). MATERIALS AND METHODS: The test results of 24 ON patients were compared with those obtained in 40 normal control subjects. MfVEP recordings were obtained by using an Optoelectronic Stimulator that extracts topographic VEP using a pseudorandom m-sequence stimulus. Receiver operator characteristic (ROC) curves were calculated to determine the sensitivity and specificity of abnormal values. RESULTS: The frequency of the abnormal ocular findings differed in the ON patients according to the used technique. Reduced visual sensitivity was demonstrated in 12 eyes (54.5%) using FDT perimetry; 17 eyes (77.2%) showed decreased amplitude and/or an increase in the implicit time of the P1 wave in mfVEP and 20 eyes (90.9%) showed an abnormal decrease in the amplitude and/or an increase in the latency of the P100 peak at VEP examination. The areas under the ROC curves ranged from 0.743 to 0.935, with VEP having the largest areas. The VEP and mfVEP amplitudes and latencies yielded the greatest sensitivity and specificity. CONCLUSIONS: The mfVEP and the FDT perimetry can be used for the evaluation and monitoring of visual impairment in patients with ON. The most sensitive and practical diagnostic tool in patients with ON is, however, the traditional VEP. The mfVEP can be utilized in those cases with doubtful or negative VEP results.

MP-1 biofeedback: luminous pattern stimulus versus acoustic biofeedback in age related macular degeneration (AMD).

In this study we evaluated the efficacy of visual rehabilitation by means of two different types of biofeedback techniques in patients with age related macular degeneration (AMD). Thirty patients, bilaterally affected by AMD, were randomly divided in two groups: one group was treated with an acoustic biofeedback (AB group), the other was treated with luminous biofeedback of a black and white checkerboard flickering during the examination (LB group). All patients underwent a complete ophthalmological examination. Rehabilitation consisted of 12 training sessions of 10 min for each eye performed once a week for both groups. Both groups showed better visual performance after rehabilitation and luminous flickering biofeedback stimulus showed a statistically significant improvement in training the patients to modify their preferred retinal locus in comparison to acoustic biofeedback. This suggests that it might be possible in the damaged retina to override dead photoreceptor and outer retinal layers and involve residual surviving cells, as well as amplify and integrate retinal and brain cortex plasticity by using other spared channels towards associative pathways.

BBS1 mutations in a wide spectrum of phenotypes ranging from nonsyndromic retinitis pigmentosa to Bardet-Biedl syndrome.

OBJECTIVE: To investigate the involvement of the Bardet-Biedl syndrome (BBS) gene BBS1 p.M390R variant in nonsyndromic autosomal recessive retinitis pigmentosa (RP). METHODS: Homozygosity mapping of a patient with isolated RP was followed by BBS1 sequence analysis. We performed restriction fragment length polymorphism analysis of the p.M390R allele in 2007 patients with isolated RP or autosomal recessive RP and in 1824 ethnically matched controls. Patients with 2 BBS1 variants underwent extensive clinical and ophthalmologic assessment. RESULTS: In an RP proband who did not fulfill the clinical criteria for BBS, we identified a large homozygous region encompassing the BBS1 gene, which carried the p.M390R variant. In addition, this variant was detected homozygously in 10 RP patients and 1 control, compound heterozygously in 3 patients, and heterozygously in 5 patients and 6 controls. The 14 patients with 2 BBS1 variants showed the entire clinical spectrum, from nonsyndromic RP to full-blown BBS. In 8 of 14 patients, visual acuity was significantly reduced. In patients with electroretinographic responses, a rod-cone pattern of photoreceptor degeneration was observed. CONCLUSIONS: Variants in BBS1 are significantly associated with nonsyndromic autosomal recessive RP and relatively mild forms of BBS. As exemplified in this study by the identification of a homozygous p.M390R variant in a control individual and in unaffected parents of BBS patients in other studies, cis - or trans -acting modifiers may influence the disease phenotype. CLINICAL RELEVANCE: It is important to monitor patients with an early diagnosis of mild BBS phenotypes for possible life-threatening conditions.

The Mozart effect in biofeedback visual rehabilitation: a case report.

PURPOSE: To evaluate the usefulness of acoustic biofeedback by means of Mozart's Sonata for Two Pianos in D Major K. 448 to maintain and/or restore visual performance in a patient with macular pucker and glaucoma. METHODS: A 74-year-old patient with open angle glaucoma in both eyes and macular pucker in the right eye (RE) underwent visual rehabilitation with acoustic biofeedback by means of the MAIA™ Vision Training Module (Centervue, Padova, Italy) 10 minutes each eye once a week for 5 weeks. The patient was asked to move his eyes according to a sound which changed into Mozart's Sonata for Two Pianos when the patient locked the fixation target. RESULTS: Best-corrected visual acuity improved in his right eye (RE) and was stable in the left eye (LE). Fixation stability improved in both eyes, and retinal sensitivity decreased in the RE and improved in the LE. The characteristic of the macular pucker did not change during the training as demonstrated with optical coherence tomography. The patient was very satisfied with the training, as demonstrated by a 25-item questionnaire (National Eye Institute - Visual Functioning Questionnaire, NEI-VFQ-25). The patient's reading speed and the character size which he was able to read improved in his RE. CONCLUSION: Music could enhance synaptic plasticity and affect neural learning and fixation training by means of MAIA vision training. Therefore it can improve visual performance in patients with macular pucker, postpone the surgical time, and assure a better quality of life for the patient.

Low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular diseases: a pilot study.

Macular disease is one of the main causes of visual impairment. We studied the efficacy of low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular disease. Five patients were enrolled (3 female and 2 male, mean age 53.8 years) and a total of 9 eyes was examined: 2 eyes with vitelliform dystrophy, 1 with a post-traumatic macular scar, 2 with Stargardt disease, 2 with myopic macular degeneration, 2 with cone dystrophy. All the patients underwent the following tests: visual acuity, reading speed, fixation test, MP-1 microperimetry. Low-vision rehabilitation, which lasted 10 weeks, consisted of 10 training sessions of 10 min for each eye, performed once a week using the MP-1 biofeedback examination. Statistical analysis was performed using Student's t-test. p values less than 0.05 were considered statistically significant. After training all patients displayed an improvement in visual acuity, fixation behaviour, retinal sensitivity and reading speed. Fixation behaviour within the 2 degrees diameter circle improved and was statistically significant for reading speed (p = 0.01). Reading speed improved from a mean value of 64.3 to 92 words/min. Our results show that audio feedback can, by increasing attentional modulation, help the brain to fix the final preferred retinal locus. Audio feedback facilitates stimuli transmission between intraretinal neurons as well as between the retina and brain, which is where the highest level of stimuli processing occurs, thereby probably supporting a "remapping phenomenon".

Use of MP-1 microperimetry in optic disc pit and secondary retinoschisis.

The optic nerve head pit is a congenital anomaly of the optic disc due to imperfect closure of the superior edge of the embryonic fissure. We studied in detail by means of fluorescein angiography (FLA), microperimetry (fundus related perimetry), and ocular coherence tomography (OCT) the case of a 30-year-old woman who had an optic pit with secondary retinoschisis in her right eye.

Microperimetric biofeedback in AMD patients.

To analyse biofeedback training by microperimeter MP-1 (Nidek Technologies) on patients with Age Related Maculopathy (AMD). We enrolled 15 patients (10 female and 5 male) and examined total of 27 eyes with AMD. All the patient underwent 10 training sessions of 10 min for each eye, performed once a week using the MP-1 biofeedback examination. Statistical analysis was performed using Student's t-test. p values less than 0.05 were considered statistically significant. All patients displayed an improvement in visual acuity, fixation behaviour, retinal sensitivity an reading speed. The mean character size value improved from 36.4 to 11.7; this result was statistically significant (p = 0.031). A biofeedback examination using the MP-1 microperimeter can help the brain to memorize the final fixation location by increasing attention modulation, thereby providing an efficient preferred retinal locus for visual tasks in patients with macular disease and central scotoma.

Acute electroretinographic changes during sildenafil (Viagra) treatment for erectile dysfunction.

The authors describe their findings on 12 subjects who were treated with 50 mg of sildenafil (Viagra) and underwent ERG measurements prior to and 1 hour after ingestion. The Naka-Rushton equation was used to describe the b-wave luminance-response function of the scotopic ERG. Statistically significant differences were noted in the Vmax and K values. Sildenafil ingestion resulted in an increase in Vmax (higher rod response to light stimuli) and a decrease in K (higher sensitivity).